This research project is designed to elucidate the mechanisms and control of intestinal development and function. Intrinsic and extrinsic regulation of intestinal enzyme activity is of particular importance, with emphasis placed on the role of intraluminal factors (diet, fasting and drugs) and hormones. In addition, since pancreatic secretions compromise an important component of the intraluminal environment, development and control of pancreatic secretion is also under study. It is the overall aim of the project to relate events occurring during fetal or early postnatal life to those found in maturity. Since intestinal enzyme activity is clearly controlled by both gene-regulated and non-genetic influences, intestinal enzyme synthesis is being studied in an effort to identify factors which regulate intracellular movement of brush border enzymes from the sites of synthesis to microvillus membrane. Studies to be performed in the coming grant year include measurements of the rates of synthesis of intestinal sucrase under a variety of experimental conditions (and during development) using immunochemical methods and mono-specific antibody to rat sucrase. In addition, sucrase synthesis as a marker for brush border integrity will be studied in a new animal model for malnutrition. Furthermore, the effects of colchicine and antinomycin on sucrase synthesis and processing will be studied. In previous studies, we have identified an enzymatically inactive sucrase precursor in crypt cells. The chemical and biochemical characteristics of this inactive precursor will be studied in comparison to the purified active enzyme in an effort to elucidate the mechanisms responsible for conversion from inactive to active protein. The role of pancreatic enzymes in controlling microvillus membrane proteins during development will also be investigated.